Cardiovascular disease accounts for half the deaths in adults undergoing regular dialysis, but the mechanisms responsible remain uncertain. Recent evidence indicates, however, that certain disturbances in mineral metabolism, and/or the therapeutic measures aimed at controlling them, contribute to the development of coronary artery and vascular calcification in patients treated with long-term hemodialysis. Coronary calcification is common in those with end-stage renal disease (ESRD), and the disturbance may account, at least in part, for the high mortality rate from cardiovascular causes in this population. The multi-center, randomized, clinical trial outlined in the current proposal is designed to assess the roles of two separate, yet potentially related, determinants of coronary artery calcification in patients with ESRD who are treated with hemodialysis. The impact of reducing the amount of calcium given orally to patients with ESRD by using sevelamer (RenaGel) rather than calcium-based compounds to control serum phosphorus will be evaluated. Coronary artery calcification will be measured by electron beam computed tomography (EBCT) before and after 12 months of treatment. In addition, the effect of lowering serum total and LDL cholesterol levels on coronary artery calcification scores will be assessed during treatment with either simvastatin or placebo to inhibit 3-hydroxyl-3-methylglutaryl Co-enzyme A reductase (HMG Co-A). Potential interactions between these two therapeutic interventions on coronary artery calcification scores will be examined using a 2 x 2 factorial study design. The primary outcome variable is the coronary artery calcification score after 12 months of treatment in each of four groups. The broad objectives of the project are to determine the efficacy of two therapeutic interventions aimed at modifying factors thought to contribute to the development and progression of coronary artery calcification, and possibly to cardiovascular mortality, in patients undergoing long-term dialysis.